1. Field of the Invention
The present invention relates to a process for an induction culture of T lymphocytes having killing activity against tumor cells. More specifically, the present invention relates to a process for cultivation by which T lymphocytes that have cell killing activities against specific tumor cells derived from a tumor patient can be extracorporeally induced and proliferated.
2. Related Art
Cytotoxic T lymphocytes (hereinafter in the specification, "cytotoxic T lymphocyte" may sometimes be referred to as "CTL") have been known as lymphocytes capable of specifically killing tumor cells. Cytotoxic T lymphocytes may be induced and proliferated from mononuclear cell fractions. The cells have extremely high specificity against tumor cells in such a manner that they, even after induction and proliferation, only attack the tumor cells used as a target for CTL induction culture, and that they can never attack other tumor cells.
For induction cultures where CTLs are induced and proliferated by using mononuclear cell fractions from peripheral blood, purely cultured established tumor cell lines or tumor cells separated from a tissue and cultured under conditions of quasi-pure culture have been so far used as the target (target cells). However, there is a problem that tumor cells obtained by using an extirpated human tumor tissue or organ as a starting material may possibly be contaminated with tissue cells other than tumor cells, and that pure cultures are not always available.
Furthermore, there is another problem that purely cultured tumor cells can hardly be established as tumor cell lines unless they are artificially immortalized by, e.g. a treatment using genetic engineering techniques, and that most of tumor cells lose proliferating abilities in subcultures. Moreover, even where a surgically extirpated tumor tissue material is used that obviously contains living tumor cells, it is sometimes observed that the tumor cells cannot be suitable to in vitro culture conditions and die in a few days after the beginning of primary culture. For these reasons, induction cultures of CTLs can not be easily obtained where the establishments of tumor cell line or the primary cultures of tumor cells are difficult. Accordingly, processes are desired by which CTLs can be reliably induced using tumor tissues.